Unveiling the Synergistic Influence of TiO₂ and Chitosan‐Based Hydrogel in Precision Surface Co‐Modification for Superior Pure Titanium Implant Performance

ABSTRACT Bacterial infections are the primary cause of surgical failures associated with orthopedic implants. One promising avenue to address this challenge and capitalize on the effectiveness of antibiotic administration involves utilizing titania nanotubes (TNTs) loaded with vancomycin (Van). Electrochemical anodization offers a contemporary approach for producing Titania‐NTs with applications in localized vancomycin delivery. However, the regulation of the drug release mechanism from these delivery systems is complex. This research delves into the controlled release of vancomycin from Titania‐NT surfaces enriched with drug/polymer through physical absorption. The loading and in vitro releases of Van were analyzed using the Korsmeyer–Peppas kinetic model (R² = 0.99), which indicated non‐Fickian diffusion (case II/I, n = 0.41). Antibacterial activity was tested against Staphylococcus aureus and Pseudomonas aeruginosa through turbidity measurements, CFU counts, and agar disc diffusion assays. Protein adsorption on titanium surfaces was evaluated, and gene expression analysis was performed to assess osteogenic markers (ALP and OCN). Vancomycin‐loaded TNTs (11 μM) stimulated MC3T3‐E1 cell proliferation, demonstrating enhanced cell viability. The presence of chitosan effectively controlled the Van delivery process. The morphology of anodized Ti surfaces played a key role in inhibiting bacterial growth. Results demonstrated reduced bacterial growth and significant protein adsorption on modified surfaces. Chitosan‐loaded TNTs significantly upregulated osteogenic markers ALP and OCN, with T60‐van/chit‐20 showing the highest expression levels, enhancing osteogenic differentiation and bone integration.